An epoxytriazole derivative represented by formula (2):
(wherein R represents a hydrogen atom or C1-12 alkyl group and Ar represents an aromatic group optionally substituted by a halogen atom(s) or a trifluoromethyl group(s)),is a synthetic intermediate for a triazole compound which is useful as an antifungal agent (e.g., JP-H05-230038A, JP-H04-356471A). It is known that the epoxytriazole derivative is prepared by a process comprising a step of making an epoxy compound represented by formula (1z):
(wherein X″ represents an optionally protected hydroxy group or leaving group, and R and Ar are defined above),react with 1,2,4-triazole in the presence of a base.For example, proposed are a process of the reaction using a water-prohibitive base such as sodium hydride and potassium tert-butoxide (e.g., JP-H04-74168A, WO2004/000826A, JP-2001-48873A, WO99/29675A, Chemical & Pharmaceutical Bulletin, 1992, Vol.40, No.2, p. 562-564), a process of the reaction in an aprotic solvent such as dimethyl sulfoxide and N,N-dimethylformamide dissolving potassium carbonate, potassium hydroxide or the like (e.g., WO2004/018486A, JP-H05-213906A, Heterocycles, 1998, Vol.49, p. 181-190) and a process of the reaction using a solid metal salt of 1,2,4-triazole prepared from a base and 1,2,4-triazole.
In the process using a water-prohibitive base, anhydrous solvent is required for the reaction and the process should be strictly controlled of moisture since the base is water-prohibitive. Further, even in the process of the reaction in the aprotic solvent dissolving potassium carbonate, potassium hydroxide or the like, an anhydrous base and anhydrous solvent are required. Furthermore, in the process of the reaction using a solid metal salt of 1,2,4-triazole, it is required that the metal salt of 1,2,4-triazole should be prepared from a base and 1,2,4-triazole and isolated in advance, and the steps including filtration and transport of powders or slurry are troublesome.